This application is for renewed support of an ongoing program of study on the physicochemical and biological properties of proteins and peptides in solution with emphasis on their interaction with each other and with small molecules. The following research is proposed: (a) The molecular mechanisms whereby chlorpromazine (Thorazine) reversibly inhibits the repolymerization of tubulin into microtubules and the specific binding of colchicine by tubulin will be investigated by the combined application of the Hummel-Dreyer method, for quantitating the reversible binding of chlorpromazine by purified tubulin; ultracentrifugation; CD; and electron microscopy. (b) Our CD and C13 NMR studies on the solution conformation of bradykinin and its analogs will be continued and extended to include its interaction with receptor sites on smooth muscle and an attempt to purify the receptor. (c) The contribution of intramolecular hydrogen bonding to the conformation of luteinizing hormone releasing hormone and its analogs and peptide fragments will be assessed by CD. (d) The solution conformation of Lys-Lys-Lys and certain other tripeptides will be examined by the combined application of CD and C13 NMR. (e) Our theoretical calculations on the mass transport of interacting macromolecules will be continued and extended to include the Hummel-Dreyer method as applied to ligand-mediated dimerization; sedimentation of ligand-facilitated as opposed to ligand-mediated dimerization; and electrofocusing of interacting macromolecules.